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Analysis of radiation-induced cell death in head and neck squamous cell carcinoma and rat liver maintained in microfluidic devices

Green, Victoria L.; Greenman, John; Carr, Simon D.; Stafford, Nicholas D.

Authors

Victoria L. Green

Simon D. Carr

Nicholas D. Stafford

Abstract

Objective The aim of this study was to investigate how head and neck squamous cell carcinoma (HNSCC) tissue biopsies maintained in a pseudo in vivo environment within a bespoke microfluidic device respond to radiation treatment. Study Design Feasibility study. Setting Tertiary referral center. Subjects and Methods Thirty-five patients with HNSCC were recruited, and liver tissue from 5 Wistar rats was obtained. A microfluidic device was used to maintain the tissue biopsy samples in a viable state. Rat liver was used to optimize the methodology. HNSCC was obtained from patients with T1-T3 laryngeal or oropharyngeal SCC; N1-N2 metastatic cervical lymph nodes were also obtained. Irradiation consisted of single doses of between 2 Gy and 40 Gy and a fractionated course of 5×2 Gy. Cell death was assessed in the tissue effluent using the soluble markers lactate dehydrogenase (LDH) and cytochrome c and in the tissue by immunohistochemical detection of cleaved cytokeratin18 (M30 antibody). Results A significant surge in LDH release was demonstrated in the rat liver after a single dose of 20 Gy; in HNSCC, it was seen after 40 Gy compared with the control. There was no significant difference in cytochrome c release after 5 Gy or 10 Gy. M30 demonstrated a dose-dependent increase in apoptotic index for a given increase in single-dose radiotherapy. There was a significant increase in apoptotic index between 1×2 Gy and 5×2 Gy. Conclusion M30 is a superior method compared with soluble markers in detecting low-dose radiation-induced cell death. This microfluidic technique can be used to assess radiation-induced cell death in HNSCC and therefore has the potential to be used to predict radiation response.

Publication Date 2014-01
Journal Otolaryngology - head and neck surgery
Print ISSN 0194-5998
Electronic ISSN 1097-6817
Publisher SAGE Publications
Peer Reviewed Peer Reviewed
Volume 150
Issue 1
Pages 73-80
Institution Citation Green, V. L., Greenman, J., Carr, S. D., & Stafford, N. D. (2014). Analysis of radiation-induced cell death in head and neck squamous cell carcinoma and rat liver maintained in microfluidic devices. Otolaryngology and head and neck surgery, 150(1), 73-80. https://doi.org/10.1177/0194599813507427
DOI https://doi.org/10.1177/0194599813507427
Keywords Microfluidic techniques, Radiotherapy, Head and neck squamous cell carcinoma, Rat liver
Publisher URL http://oto.sagepub.com/content/150/1/73
Copyright Statement ©2015 University of Hull
Additional Information Copy of article first published in: Otolaryngology - head and neck surgery, 2014, v.150, issue 1.

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